共查询到20条相似文献,搜索用时 15 毫秒
1.
Interleukin-17: a mediator of inflammatory responses 总被引:14,自引:0,他引:14
Interleukin-17 (IL-17) is a prototype member of a new cytokine family with six species identified to date. IL-17 is secreted mainly by activated CD4+ and CD8+ T lymphocytes, while its receptor is distributed ubiquitously. IL-17 has been classified as a proinflammatory cytokine because of its ability to induce the expression of many mediators of inflammation, most strikingly those that are involved in the proliferation, maturation and chemotaxis of neutrophils. Increased levels of IL-17 have been associated with several conditions, including airway inflammation, rheumatoid arthritis, intraperitoneal abscesses and adhesions, inflammatory bowel disease, allograft rejection, psoriasis, cancer and multiple sclerosis. This review provides an overview of IL-17 activities, concentrating on those that lead to neutrophil recruitment.Received 13 June 2003; received after revision 27 August 2003; accepted 1 September 2003 相似文献
2.
A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant,op/op mice were studied histologically. GMG cell differentiation appeared to progress normally inop/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient inop/op mice. 相似文献
3.
Dong Gao Ruipeng Wang Bingfeng Li Yongkang Yang Zhonghe Zhai Dan-Ying Chen 《Cellular and molecular life sciences : CMLS》2009,66(15):2573-2584
Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways
activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth
factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB
by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40
domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding
protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression
and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced
but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation
by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation
pathway.
D. Gao and R. Wang contributed equally to this work. 相似文献
4.
Patricia J. Lardone Amalia Rubio Isabel Cerrillo Araceli G��mez-Corvera Antonio Carrillo-Vico Marina Sanchez-Hidalgo Juan M. Guerrero Patricia Fernandez-Riejos Victor Sanchez-Margalet Patrocinio Molinero 《Cellular and molecular life sciences : CMLS》2010,67(18):3163-3172
Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing
the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established
an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT1 receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels
of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation
with lectin. Likewise, tetracycline-inducible stable cell line expressing MT1 antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT1 cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface.
The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation. 相似文献
5.
Interleukin (IL)-1 is a proinflammatory cytokine with important roles in innate immunity, as well as in normal tissue homeostasis.
Interestingly, recent studies have also shown IL-1 to function in the dynamics of the actin cytoskeleton and cell junctions.
For example, treatment of different epithelia with IL-1α often results in the restructuring of the actin network and cell
junctions, thereby leading to junction disassembly. In this review, we highlight new and interesting findings that show IL-1
to be a critical player of restructuring events in the seminiferous epithelium of the testis during spermatogenesis. 相似文献
6.
Elisabetta Rovida Persio Dello Sbarba 《Cellular and molecular life sciences : CMLS》2014,71(19):3627-3631
Receptor tyrosine kinases (RTK) have long being studied with respect to the “canonical” signaling. This includes ligand-induced activation of a receptor tyrosine kinase at the cell surface that leads to receptor dimerization, followed by its phosphorylation in the intracellular domain and activation. The activated receptor then recruits cytoplasmic signaling molecules including other kinases. Activation of the downstream signaling cascade frequently leads to changes in gene expression following nuclear translocation of downstream targets. However, RTK themselves may localize within the nucleus, as either full-length molecules or cleaved fragments, with or without their ligands. Significant differences in this mechanism have been reported depending on the individual RTK, cellular context or disease. Accumulating evidences indicate that the colony-stimulating factor-1 receptor (CSF-1R) may localize within the nucleus. To date, however, little is known about the mechanism of CSF-1R nuclear shuttling, as well as the functional role of nuclear CSF-1R. 相似文献
7.
8.
Se Hwan Mun Na Young Ko Hyuk Soon Kim Jie Wan Kim Do Kyun Kim A-Ram Kim Seung Hyun Lee Yong-Gil Kim Chang Keun Lee Seoung Hoon Lee Bo Kyung Kim Michael A. Beaven Young Mi Kim Wahn Soo Choi 《Cellular and molecular life sciences : CMLS》2010,67(22):3883-3892
Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes. 相似文献
9.
A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant, op/op mice were studied histologically. GMG cell differentiation appeared to progress normally in op/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient in op/op mice. 相似文献
10.
L. Adorini 《Cellular and molecular life sciences : CMLS》1999,55(12):1610-1625
Interleukin 12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (APCs) which plays a key
role in promoting type 1 T helper cell (Th1) responses. The powerful activity of IL-12 requires tight control, which is exerted
at various levels. Primary control is exerted on IL-12 production by APCs, a major factor driving the response towards the
Th1 or Th2 phenotype. Another level of control regulates expression of the IL-12 receptor (IL-12R), which is composed of two
subunits, β1 and β2. The IL-12R β2 subunit has signal-transducing capacity and modulation of its expression is central to
the regulation of IL-12 responsiveness. Endogenous IL-12 plays an important role in host defense against infection by a variety
of intracellular pathogens. Its Th1-promoting activity, however, also favors Th1-mediated immunopathology and, in particular,
the induction of Th1-mediated autoimmune diseases.
Received 15 January 1999; received after revision 11 March 1999; accepted 16 March 1999 相似文献
11.
M. Maes W. Stevens S. Scharpe E. Bosmans F. De Meyer P. D'Hondt D. Peeters P. Thompson P. Cosyns L. De Clerck C. Bridts H. Neels A. Wauters W. Cooreman 《Cellular and molecular life sciences : CMLS》1994,50(9):821-829
This study has been carried out in order to investigate seasonal variation in peripheral blood immune cells, such as leukocytes, monocytes, neutrophils, lymphocytes, CD3+ T, CD4+ T, CD8+ t, CD25+ T, CD20+ B, and serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers. Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood samplings during one calendar year for peripheral blood count, flow cytometric enumeration of peripheral leukocyte subsets and immunoassays of IL-6, sIL-6R and sIL-2R. It was found that most of the immune variables change rhythmically during the seasons as a group phenomenon. Statistically significant yearly variations with seasonal rhythms, i.e. annual rhythms or harmonics, such as semiannual, tetramensual and trimensual rhythms, were found in the number of leukocytes, neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in the CD4+/CD8+ ratio, and serum IL-6 and sIL-6R levels. It is concluded that the immune system is characterized by a multifrequency time-structure with significant high-amplitude yearly variations in the number of some peripheral blood leukocyte subsets. 相似文献
12.
Miriam Beer Torchinsky J. Magarian Blander 《Cellular and molecular life sciences : CMLS》2010,67(9):1407-1421
In the few years since their discovery, T helper 17 cells (TH17) have been shown to play an important role in host defense against infections, and in tissue inflammation during autoimmunity.
TH17 cells produce IL-17, IL-21, IL-10, and IL-22 cytokines, and thus have broad effects on a variety of tissues. Notably, the
requirement for the immunosuppressive cytokine TGF-β along with the pro-inflammatory cytokine IL-6 for TH17 differentiation supports the intimate relationship between the TH17 subset and FOXP3+ regulatory T cells. Here, we discuss current knowledge on effector functions and differentiation of the TH17 lineage. Furthermore, we now know of a physiological stimulus for TH17 differentiation: innate immune recognition of cells undergoing apoptosis as a direct result of infection induces unique
development of this subset. As our knowledge of TH17 and T regulatory cells grows, we are building on a new framework for the understanding of effector T cell differentiation
and the biology of CD4+ T cell adaptive immune responses. 相似文献
13.
Boyman O Krieg C Homann D Sprent J 《Cellular and molecular life sciences : CMLS》2012,69(10):1597-1608
Homeostasis in the immune system encompasses the mechanisms governing maintenance of a functional and diverse pool of lymphocytes, thus guaranteeing immunity to pathogens while remaining self-tolerant. Antigen-naïve T cells rely on survival signals through contact with self-peptide-loaded major histocompatibility complex (MHC) molecules plus interleukin (IL)-7. Conversely, antigen-experienced (memory) T cells are typically MHC-independent and they survive and undergo periodic homeostatic proliferation through contact with both IL-7 and IL-15. Also, non-conventional γδ T cells rely on a mix of IL-7 and IL-15 for their homeostasis, whereas natural killer cells are mainly dependent on contact with IL-15. Homeostasis of CD4+ T regulatory cells is different in being chiefly regulated by contact with IL-2. Notably, increased levels of these cytokines cause expansion of responsive lymphocytes, such as found in lymphopenic hosts or following cytokine injection, whereas reduced cytokine levels cause a decline in cell numbers. 相似文献
14.
2-Carboxyethylgermanium sesquioxide,a synthetic organogermanium compound,as an inducer of contrasuppressor T cells 总被引:2,自引:0,他引:2
K. Ikemoto M. Kobayashi T. Fukumoto M. Morimatsu R. B. Pollard F. Suzuki 《Cellular and molecular life sciences : CMLS》1996,52(2):159-166
2-Carboxyethylgermanium sesquioxide (Ge-132), a synthesized organogermanium compound with immunomodulaing activities, was shown to be an inducer of anti-suppressor T cells in normal mice. The suppressor cell activity of T6S cells, a clone of burn-induced CD8+ IL-4-producing suppressor T cells, was clearly inhibited when a mixed lymphocyte-tumor cell reaction of the clone was conducted with splenic mononuclear cells from mice treated orally with a 100 mg/kg dose of Ge-132. The activity of anti-suppressor cells was demonstrated in spleens of mice 2 days after treatment with Ge-132 and reached its peak on day 3. The anti-suppressor cells induced by the compound were of a contrasuppressor T cell-linage, because they were characterized as CD4+ CD28+ TCR/+
Vicia villosa lectin-adherent T cells. These cells produced IFN- but did not produce IL-2, IL-4, IL-6 or IL-10 in their culture fluids. CD4+ anti-suppressor T cells induced by Ge-132 may be different from other subsets of CD4+ T cells because Th1 and Th2 cells generated in our laboratory did not adhere toVicia villosa lectin-coated petri dishes, and each produced specific cytokines. Th1 cells produced IFN- and IL-2 while Th2 cells produce IL-4 and IL-10 in vitro. These results suggest that Ge-132 may be useful as an inducer of contrasuppressor T cells in immunocompromised individuals bearing suppressor T cells. To eliminate suppressor T cells from immunocompromised hosts may result in improved resistance from various opportunistic infections. 相似文献
15.
Iva Hafner-Bratkovi? Mojca Ben?ina Katherine A. Fitzgerald Douglas Golenbock Roman Jerala 《Cellular and molecular life sciences : CMLS》2012,69(24):4215-4228
Prion diseases are fatal transmissible neurodegenerative diseases, characterized by aggregation of the pathological form of prion protein, spongiform degeneration, and neuronal loss, and activation of astrocytes and microglia. Microglia can clear prion plaques, but on the other hand cause neuronal death via release of neurotoxic species. Elevated expression of the proinflammatory cytokine IL-1β has been observed in brains affected by several prion diseases, and IL-1R-deficiency significantly prolonged the onset of the neurodegeneration in mice. We show that microglial cells stimulated by prion protein (PrP) fibrils induced neuronal toxicity. Microglia and macrophages release IL-1β upon stimulation by PrP fibrils, which depends on the NLRP3 inflammasome. Activation of NLRP3 inflammasome by PrP fibrils requires depletion of intracellular K+, and requires phagocytosis of PrP fibrils and consecutive lysosome destabilization. Among the well-defined molecular forms of PrP, the strongest NLRP3 activation was observed by fibrils, followed by aggregates, while neither native monomeric nor oligomeric PrP were able to activate the NLRP3 inflammasome. Our results together with previous studies on IL-1R-deficient mice suggest the IL-1 signaling pathway as the perspective target for the therapy of prion disease. 相似文献
16.
Monica Bari Tiziana Bonifacino Marco Milanese Paola Spagnuolo Simona Zappettini Natalia Battista Francesco Giribaldi Cesare Usai Giambattista Bonanno Mauro Maccarrone 《Cellular and molecular life sciences : CMLS》2011,68(5):833-845
The endocannabinoid system and endocannabinoid receptor-driven modulation of glutamate release were studied in rat brain cortex
astroglial gliosomes. These preparations contained the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, as well their major biosynthetic (N-acyl-phosphatidylethanolamines-hydrolyzing-phospholipase D and diacylglycerol-lipase) and catabolic (fatty acid amide-hydrolase
and monoacylglycerol-lipase) enzymes. Gliosomes expressed type-1 (CB1R), type-2 (CB2R) cannabinoid, and type-1 vanilloid (TRPV1)
receptors, as ascertained by Western blotting and confocal microscopy. Methanandamide, a stable analogue of anandamide acting
as CB1R, CB2R, and TRPV1 agonist, stimulated or inhibited the depolarization-evoked gliosomal [3H]d-aspartate release, at lower and higher concentrations, respectively. Experiments with ACEA (arachidonyl-2′-chloroethylamide),
JWH133 ((6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]-pyran) and capsaicin, selective
agonists at CB1R, CB2R and TRPV1, respectively, demonstrated that potentiation of [3H]d-aspartate release was due to CB1R while inhibition to CB2R and TRPV1 engagement. These findings were confirmed by using selective
receptor antagonists. Furthermore, CB1R activation caused increase of intracellular IP3 and Ca2+ concentration, suggesting an involvement of phospholipase C. 相似文献
17.
The induction of lymphokine-activated killer (LAK) cells from natural killer (NK) lineage cells by interleukin-4 (IL-4) was studied in vitro. Activation of nude mouse spleen cells by IL-4 generated cytotoxic cells, capable of killing NK-sensitive as well as NK-resistant tumor cells. The induction of peak lytic activity was demonstrated after 3 days of culture with IL-4. Surface marker analysis indicated that the majority of precursor cells were aGM1+, Thy1–, and the majority of effector cells were aGM1+, Thy1+, suggesting that IL-4 induced LAK cells from nude mouse spleen cells were similar to those from normal mouse spleen cells. The induction of nude mouse LAK cells by IL-4 was partially inhibited by anti-IL-4 or anti-interferon (IFN)-, antibody, and it was further inhibited by the combination of two antibodies, suggesting that IFN-, production was associated with LAK induction of NK lineage cells by IL-4. 相似文献
18.
Emanuela Talamonti Anna M. Pauter Abolfazl Asadi Alexander W. Fischer Valerio Chiurchiù Anders Jacobsson 《Cellular and molecular life sciences : CMLS》2017,74(15):2815-2826
Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1 and M2 macrophages obtained from mice deficient of Elovl2 (Elovl2?/?), a key enzyme for DHA synthesis in mammals. Although both wild type and Elovl2?/? mice were able to generate efficient M1 and M2 macrophages, M1 cells derived from Elovl2?/? mice showed an increased expression of key markers (iNOS, CD86 and MARCO) and cytokines (IL-6, IL-12 and IL-23). However, M2 macrophages exhibited upregulated M1-like markers like CD80, CD86 and IL-6, concomitantly with a downregulation of their signature marker CD206. These effects were counteracted in cells obtained from DHA-supplemented animals. Finally, white adipose tissue of Elovl2?/? mice presented an M1-like pro-inflammatory phenotype. Hence, impairment of systemic DHA synthesis delineates an alteration of M1/M2 macrophages both in vitro and in vivo, with M1 being hyperactive and more pro-inflammatory while M2 less protective, supporting the view that DHA has a key role in controlling the balance between pro- and anti-inflammatory processes. 相似文献
19.
Wang R Han G Wang J Chen G Xu R Wang L Li X Shen B Li Y 《Cellular and molecular life sciences : CMLS》2008,65(23):3851-3860
Interleukin (IL)-27 is an IL-12-related cytokine that can promote both anti- and pro-inflammatory immune responses. This study
investigated the potential role of IL-27 in autoimmune diabetes. We detected a high level of IL-27 in diabetic NOD mice. In
addition, blockade of IL-27 significantly delayed the onset of diabetic splenocyte-transferred diabetes, while IL-27-treated
diabetic splenocytes promoted the onset of the disease, compared with untreated controls. Furthermore, IL-27 up-regulated
pro-inflammatory cytokines IFN-γ and IL-17 and down-regulated anti-inflammatory cytokines IL-4, TGF-β, and IL-10 secreted
by diabetic splenocytes. These results demonstrate a pathogenic role of IL-27 in T cell-mediated autoimmune diabetes.
Received 02 September 2008; received after revision 27 September 2008; accepted 01 October 2008
R. Wang, G. Han: These authors contributed equally to this work. 相似文献
20.
Zhang Z Zhang ZY Fauser U Schluesener HJ 《Cellular and molecular life sciences : CMLS》2008,65(24):4055-4065
Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects.
We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA
(300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed
mRNA levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and IL-17 in the lymph nodes of EAN
rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3+ cells were increased but IL-17+ cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated
both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity
and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting
that VPA could be a potent candidate for treatment of autoimmune neuropathies. 相似文献